Fraction Dose Escalation of Hypo-fractionated Radiotherapy in LANSCLC
Phase 1
Completed
- Conditions
- Locally Advanced Lung Carcinoma
- Interventions
- Radiation: Hypofractionated radiotherapyDrug: Concurrent chemotherapyDrug: Consolidation immunotherapy
- Registration Number
- NCT04951063
- Lead Sponsor
- Sun Yat-sen University
- Brief Summary
This Phase 1 trial aimed to determine the maximum tolerated fraction dose (MTD) of hypofractionated radiotherapy (hypo-RT) combined with concurrent chemotherapy and subsequent consolidation immune checkpoint inhibitors (cICI) for patients with locally advanced non-small cell lung cancer (LA-NSCLC).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 18
Inclusion Criteria
- Non-small cell lung cancer confirmed by histology.
- Tumor size is measured according to RECIST standard.
- Unresectable stage IIIA (N2) and IIIB/IIIC, confirmed by PET-CT/or chest and abdomen CT, brain MRI, and whole body bone scan.
- 18-75 years old, regardless of gender.
- The ECOG score is 0-1.
- Newly treated or underwent neoadjuvant chemotherapy and/or immunotherapy.
- Have not received chest radiotherapy in the past.
- Serum hemoglobin ≥10 mg/dL, platelets ≥100000/μL, absolute neutrophil count ≥1500/μL.
- Serum creatinine ≤1.25 times UNL or creatinine clearance ≥60 ml/min.
- Serum bilirubin ≤1.5 times UNL, AST (SGOT) and ALT (SGPT) ≤2.5 times UNL, alkaline phosphatase≤ 5 times UNL.
- FEV1>1 L.
- CB6 normal range.
- The patient and his family members agree and sign an informed consent form.
Exclusion Criteria
- Other malignant tumors in the past or during treatment, except for non-melanoma of the skin or carcinoma in situ of the cervix.
- Any other diseases or conditions are contraindications to chemotherapy (such as active infection, within 6 months after myocardial infarction, symptomatic heart disease, including unstable angina, congestive heart failure or uncontrolled arrhythmia, immunosuppressive therapy).
- Pregnant or breastfeeding women, women who have not undergone a pregnancy test (within 14 days before the first dose), and pregnant women.
- Those who are pregnant, breastfeeding or have fertility but have not taken contraceptive measures.
- People with bleeding tendency.
- Those who participated in other clinical trials within 30 days before participating in this experiment.
- Drug addiction, long-term alcoholism, and AIDS patients.
- People with uncontrollable seizures or loss of self-control due to mental illness.
- People with a history of severe allergies or specific physique.
- The researcher believes that the patient is inappropriate to participate in this trial.
Exit criteria
- The treatment cannot be carried out in accordance with the requirements of the research protocol;
- The patient has an allergic reaction ≥ grade 4 or a serious adverse reaction to the study drug;
- The patient is pregnant or has not used adequate contraceptive measures;
- The researcher judges that the patient should not continue to participate the clinical trial;
- The subject asked to withdraw.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Split-course adaptive HRT-CHT Hypofractionated radiotherapy In keeping the same total radiation dose (60Gy), we escalate the fraction dose to find the maximum tolerable fraction dose. 1. Level 1: DT 4500cGy/15 daily fractions/300cGy in the first course，DT 1500cGy/5 daily fractions/300cGy in the second course; 2. Level 2: DT 4000cGy/10 daily fractions/400cGy in the first course， DT 2000cGy/5 daily fractions/400cGy in the second course; 3. Level 3: DT 3000cGy/6 daily fractions/500cGy in the first course， DT 3000cGy/6 daily fractions/500cGy in the second course. RT is delivered using the IMRT technique with daily cone-beam CT image guidance. The dose limitation of organ at risk (OAR) are shown in Table 1. Patients receive a weekly infusion of docetaxel (25mg/m2) and cisplatin (25mg/m2) during RT. Consolidative immunotherapy (PD-1 or PD-L1 inhibitor) up to 1 year is administered for those without disease progression after HRT-CHT. Split-course adaptive HRT-CHT Consolidation immunotherapy In keeping the same total radiation dose (60Gy), we escalate the fraction dose to find the maximum tolerable fraction dose. 1. Level 1: DT 4500cGy/15 daily fractions/300cGy in the first course，DT 1500cGy/5 daily fractions/300cGy in the second course; 2. Level 2: DT 4000cGy/10 daily fractions/400cGy in the first course， DT 2000cGy/5 daily fractions/400cGy in the second course; 3. Level 3: DT 3000cGy/6 daily fractions/500cGy in the first course， DT 3000cGy/6 daily fractions/500cGy in the second course. RT is delivered using the IMRT technique with daily cone-beam CT image guidance. The dose limitation of organ at risk (OAR) are shown in Table 1. Patients receive a weekly infusion of docetaxel (25mg/m2) and cisplatin (25mg/m2) during RT. Consolidative immunotherapy (PD-1 or PD-L1 inhibitor) up to 1 year is administered for those without disease progression after HRT-CHT. Split-course adaptive HRT-CHT Concurrent chemotherapy In keeping the same total radiation dose (60Gy), we escalate the fraction dose to find the maximum tolerable fraction dose. 1. Level 1: DT 4500cGy/15 daily fractions/300cGy in the first course，DT 1500cGy/5 daily fractions/300cGy in the second course; 2. Level 2: DT 4000cGy/10 daily fractions/400cGy in the first course， DT 2000cGy/5 daily fractions/400cGy in the second course; 3. Level 3: DT 3000cGy/6 daily fractions/500cGy in the first course， DT 3000cGy/6 daily fractions/500cGy in the second course. RT is delivered using the IMRT technique with daily cone-beam CT image guidance. The dose limitation of organ at risk (OAR) are shown in Table 1. Patients receive a weekly infusion of docetaxel (25mg/m2) and cisplatin (25mg/m2) during RT. Consolidative immunotherapy (PD-1 or PD-L1 inhibitor) up to 1 year is administered for those without disease progression after HRT-CHT.
- Primary Outcome Measures
Name Time Method the maximally tolerated fraction dose 1 year The maximum tolerated fraction dose was defined as the highest DL in which \<=2 patients of the 6 treated patients experienced G3+ toxicity and \<=1 patient experienced G4+ toxicity within 12 months after RT. If a patient had multiple types of toxicities, only the highest grade of toxicity was counted.
- Secondary Outcome Measures
Name Time Method Overall survival 1-year Objective response rate 2 months after radiotherapy Proportion of patients with PR and CR at 2 months after radiotherapy
Progression-free survival 1-year Distant-metastasis free survival 1-year Loco-regional recurrence-free survival 1-year
Trial Locations
- Locations (1)
Sun yat-sen University Cancer Center
🇨🇳Guangzhou, Guangdong, China